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INTRODUCTION: Opioid overdose is now the leading cause of injury-related death in the United States. Over prescription of opioids is one factor contributing to this epidemic. Previous studies demonstrated an over prescription of opioids, compared to patient consumption, following general surgery procedures. The objective of this study is to evaluate opioid consumption following carotid revascularization. METHODS: This is a retrospective review of the opioid prescribing habits following discharge of carotid revascularization. Patients who were documented to receive an opioid prescription were included in the study. A phone survey was conducted to determine patient consumption of the prescribed pills. Surgical procedures include carotid endarterectomy (CEA) and transcarotid arterial revascularization (TCAR). The primary outcome is the difference between opioids prescribed and opioids consumed. RESULTS: There were 209 patients available for inclusion. The mean age was 68 years with white (98%) males (58%) making up most patients. CEA and TCAR accounted for 75% and 25% of cases, respectively. 98 (47%) patients were prescribed opioids following discharge. 8 were excluded from analysis (3 for prior opioid use, 5 declined participation). 71% of patients participated in the survey. A total of 1623 pills were prescribed (25.4 ±5.5 per patient), but only 336 pills consumed (5.3 ±1.1 per patient). 1287 (79% of total) pills were not consumed. CONCLUSION: These data are the first to compare opioid prescription with opioid consumption following carotid revascularization. We demonstrate that patients consume much less opioids than prescribed. These findings indicate that a reduction in opioid prescriptions may be possible following carotid revascularization.

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A novel and efficient formal [4 + 2+1] annulation of aryl methyl ketones and 2-aminobenzyl alcohols for the synthesis of benzo[e][1,4]diazepin-3-ones is reported. This reaction successfully affords diverse seven-membered ring lactams via dual C-O bond cleavage. A preliminary mechanistic study showed that a multicomponent dicyclization and ring-opening sequence might occur, with the introduction of methyl sulfide proposed as the last step. This efficient strategy with mild reaction conditions and a broad substrate scope has potential applications in chemistry and medicine.

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The terphenyl substructure of the chiral cyclophane natural product bazzanin K was constructed. The key step involved sequential Suzuki couplings of a non-symmetric dibromobenzene, which can be performed as a two-step process or as a one-pot three-component coupling. The key step represented a regioselective coupling of a dibromobenzene, as well as a chemoselective coupling of phenyl bromides in the presence of phenyl chlorides. Terphenyl intermediates displayed atropdiastereoisomerism, and they were converted to a single phenanthrene target by way of ring-closing metathesis.

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Degenerative changes to rotator cuff tendons are often diagnosed in elderly patients. Spontaneous healing of degenerative tendons is rather inefficient as a result of the lack of a suitable microenvironment for tendon stem cell differentiation and vascularization. Herein, multilayer hyaluronic acid/chitosan (HA/CS) nanofilms were assembled by a layer-by-layer assembly method onto aligned poly(Îµ-caprolactone) (PCL) nanofibers for use in healing degenerative tendons. Materials testing showed that the number of layers of HA/CS nanofilms could adjust the hydrophilicity and wettability of the nanofibrous membranes. In vitro, the optimal 8-layer (termed as 8LP) membrane afforded aligned morphology of tendon stem/progenitor cells (TSPCs) and up-regulated mRNA expression of tenogenic markers (SCX, BGN). In a rabbit model with disorganized rotator cuff tendons, the 8LP group up-regulated mRNA levels of collagen I/III and tenascin (TNC) at 6 weeks, but not 12 weeks, post-surgery as compared to the native PCL group. Next, vascular endothelial growth factor-loaded 8LP (termed as 8LP-V) was prepared. Compared to 8LP, 8LP-V produced higher levels of angiogenesis in the tendons at 6 or 12 weeks post-surgery, thus supplying endogenous pre-tendon growth factors (TGF-ß, IGF-1) to further enhance tenogenic transcriptional factors. As a result, 8LP-V yielded thicker collagen fibers and/or higher tendon stiffness as compared to the 8LP and clinical pericardial patch groups. This study highlights the rational design of LbL-assembled multilayer HA/CS films to upregulate tenogenesis for robust healing of degenerative rotator cuff tendons.

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Purposes: This study aimed to investigate the efficacy of ultrasound (US)-, computed tomography (CT)-, and magnetic resonance imaging (MRI)-guided radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). Materials and Methods: This retrospective study included 141 patients with HCC who were treated with US-guided (n = 29), CT-guided (n = 50), or MRI-guided RFA (n = 62). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), technique success (TS), and technique efficacy (TE). Cox model and logistic regression were used to determine the risk factors for tumor recurrence and TE. Results: The US, CT, and MRI groups did not show a significant difference in terms of baseline variables. The three groups did not differ significantly in PFS rate (P = 0.072) and OS rate (P = 0.231). The PFS rates at 3 years for the US, CT, and MRI groups were 40.90%, not reached, and 14.80%, respectively. The OS rates at 3 years were 94.70%, 97.50%, and 85.50% for US, CT, and MRI groups, respectively. No significant differences were observed between the three groups in terms of TS rate (P = 0.113) and TE rate (P = 0.682). In multivariate analysis, liver cirrhosis (P = 0.001), level of alpha-fetoprotein (AFP, P = 0.004), and number of tumors (P = 0.012) were independent risk factors for PFS. For TE, the level of AFP (P = 0.018) was an independent factor. Conclusion: US-, CT-, and MRI-guided RFA was effective for treating HCC patients. Liver cirrhosis, AFP level, and tumor number were associated with tumor recurrence, and the level of AFP was an independent risk factor affecting TE.

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Seagrass meadows are recognized as critical and among the most vulnerable habitats on the planet. As a worldwide concern, there is an urgent need to develop techniques to restore and preserve these vital coastal ecosystems due to their alarming decline rate. To effectively preserve and restore seagrasses, more research is required on the germination ecology of seeds. The seagrass Zostera japonica Asch. & Graebn is an endangered species in its native range, the Northwestern Pacific Coast. The present study investigated the germination and seedling establishment in Z. japonica seeds (collected from northern China) under different temperature and salinity conditions to explore suitable seed germination and establishment conditions, as well as the seedling formation process. Results showed that salinity had a more significant influence on seed germination rate. Germination rate decreased with an increase in salinity, and seeds did not germinate when salinity was higher than 40â¯psu. Temperature was more likely to influence germination speed, which increased with an increase in temperature, with high germination rates and the most rapid germination speed observed at 30â¯°C. Therefore, the optimal culture conditions were 10â¯psu salinity at 30â¯°C for germination and 10-20â¯psu salinity at 20â¯°C for seedling establishment, with a seed germination rate of 45.6% after 6â¯days of germination culture and a seedling establishment rate of 14.3% after 6â¯days of seedling culture, respectively. A new seedling raising method with low salinity (5â¯psu) germination and high salinity (20â¯psu) seedling establishment was proposed and a flow chart of seedling formation of Z. japonica was created. The results provide insight into the seed germination and seedling establishment in Z. japonica, and will facilitate future large-scale seedling culture and field restoration activities for this seagrass species.

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A new dineolignan, crataeguslignan A (1), along with one known dineolignan (2) were isolated from the fruits of Crataegus pinnatifida Bge. Its chemical structure was identified by comprehensive spectroscopic analyses. All the isolated compounds were investigated with regard to their Aß1-42 inhibition activity. Among them, 1 displayed the most potent Aß1-42 inhibitory ability with the inhibition rate of 85.2% at the concentration of 20 µM.

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Hyperuricemia is associated with many metabolic diseases. However, the underlying mechanism remains unknown. The gut microbiota has been demonstrated to play significant roles in the immunity and metabolism of the host. In the present study, we constructed a hyperuricemia mice model to investigate whether the metabolic disorder caused by hyperuricemia is related to intestinal dysbiosis. A significantly increased intestinal permeability was detected in hyperuricemia mice. The difference of microflora between wild type and hyperuricemia mice accompanies the translocation of gut microbiota to the extra-intestinal tissues. Such process is followed by the increase in innate immune system activation. We observed increased LPS and TNF-α in the hyperuricemia mice, indicating that hyperuricemia mice were in a low-grade systemic inflammation. In addition, hyperuricemia mice presented the early injury of parenteral tissue and the disorder of lipid metabolism. These findings suggested that intestinal dysbiosis due to impaired intestinal barrier may be the key cause of metabolic disorders in hyperuricemia mice. Our findings should aid to pave a new way of preventing and treating hyperuricemia and its complications.

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BACKGROUND: This study aims to investigate the curative effects of total hip arthroplasty (THA) in treating hip bony fusion for young and middle-aged patients with ankylosing spondylitis (AS). METHODS: The clinical data of 26 young and middle-aged patients with AS (31 coxae), who were treated with THA and followed-up for more than 3 years in the period between February 1998 and May 2013, were retrospectively analyzed. Among these patients, 22 patients were male (25 coxae) and 4 patients were female (6 coxae). Patients' age ranged within 19-50 years old, with an average of 31.5 years old. The intervals from arthroplasty to the occurrence of hip joint lesions caused by AS ranged within 2-26 years, with an average of 11.2 years. The average Harris score before the surgery was 19.0 ± 11.5 points. RESULTS: Femoral proximal cleavage fracture occurred in one coxa during the surgery and was fixed by the steel wire cerclage. Sciatic nerve traction injury occurred in one coxa after the surgery, which recovered after 6 months. Posterior hip dislocation occurred in one coxa and was immediately treated with manual reduction. All patients were followed-up, and follow-up duration ranged within 36-123 months, with an average of 46.5 months. In the last follow-up, the average Harris score was 87.1 ± 13.1 points, total passive range of motion was 215.0 ± 22.0°, and passive range of flexion was 90.8 ± 9.3°. All these indexes significantly increased compared with pretreatment (P < 0.01). A periacetabular radiolucent line occurred in one coxa with a width of < 2 mm, and no femoral radiolucent line was found during follow-ups in any patient. Heterotopic ossification occurred in four coxae. CONCLUSION: THA treatment for hip bony fusion caused by AS can achieve satisfactory hip function recovery and excellent prosthesis survival rate.

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T The cardiac glycoside digoxin was identified as a potent suppressor of PKM2-HIF-1a pathway activation in liver injury mouse models via intraperitoneal injection. We have assessed the therapeutic effects of digoxin by the clinically relevant oral route to reduce non-alcoholic steatohepatitis (NASH) in mice and analyzed the cellular basis for this effect with differential involvement of liver cell subsets. C57BL/6J male mice were placed on a high fat diet (HFD) for 10 weeks and started concurrently with the gavage of digoxin (2.5, 0.5, 0.125 mg/kg twice a week) for 5 weeks. Digoxin significantly reduced HFD-induced hepatic damage, steatosis and liver inflammation across a wide dosage range. The lowest dose of digoxin (0.125 mg/kg) showed significant protective effects against liver injury and sterile inflammation. Consistently, digoxin attenuated HIF-1a sustained NLRP3 inflammasome activation in macrophages. We have reported for the first time that PKM2 is up-regulated in hepatocytes with hepatic steatosis and digoxin directly improved hepatocyte mitochondrial dysfunction and steatosis. Mechanistically, digoxin directly bound to PKM2 and inhibited PKM2 targeting HIF-1a transactivation without affecting PKM2 enzyme activation. Thus, oral digoxin showed potential to therapeutically inhibit liver injury in NASH through the regulation of PKM2-HIF1a pathway activation with involvement of multiple cell types. Due to the large clinical experience with oral digoxin this may have significant clinical applicability in human NASH.

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BACKGROUND: Antenatal depression is a prevalent mental disorder in women who have undergone caesarean section, and it often presages adverse postoperative outcomes. Because of the lack of a laboratory-based diagnostic strategy, antenatal depression is mainly determined by a psychologist's subjective judgment based on a structured clinical interview for established diagnostic criteria. However, the diagnostic accuracy rate for depression by non-psychiatrists is relatively low. Thus, this study aimed to use lipidomics to identify potential biomarkers related to antenatal depression in women who have undergone caesarean section. METHODS: The study was designed as a matched prospective observational study. Singleton pregnant women scheduled to receive elective caesarean section, were screened for eligibility. Women diagnosed with major antenatal depression were matched with non-antenatal depression controls in terms of age (±1 year) and BMI (±1 kg/m2), and blood samples of the included matched pairs were collected. Subsequently, lipidomics of the plasma samples were performed using Ultra Performance Liquid Chromatography-mass spectrometry analysis to explore the differentially expressed lipids in women with or without antenatal depression. RESULTS: In total, 484 pregnant women were screened; 66 subjects were recruited, including 33 subjects with major antenatal depression and 33 matched controls without antenatal depression. Thirty-five differentially expressed lipid metabolites were identified (P < 0.05). The area under the receiver operating characteristic curve of these lipid metabolites was 0.7 or larger; the area under curve for cholesterol sulfate was 0.823 (95% CI: 0.716-0.930), and that of PC (18:2 (2E, 4E)/0:0) was 0.778 (95%CI: 0.662-0.895). In the conditional logistic stepwise regression analysis, cholesterol sulfate (P = 0.009) and PC (18:2 (2E, 4E)/0:0) (P = 0.035) were also identified as effective predictive risk factors for antenatal depression. CONCLUSIONS: Women who had undergone caesarean section and experienced antenatal depression presented a significantly differentially expressed profile of plasma lipidomics compared to those who did not experience antenatal depression. Cholesterol sulfate and PC (18:2 (2E, 4E)/0:0) may be effective and specific lipidic biomarkers for the prediction of antenatal depression. TRIAL REGISTRATION: China Clinical Trial Registration Center registration number: ChiCTR1800016230 ; date of registration: 21/05/2018.

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BACKGROUND AND PURPOSE: We explored the new BP thresholds and their impact on first-ever stroke risk determinations. RESULTS: During a mean following-up period of 21.85 years, 638 first-ever strokes occurred among 3906 participants. After adjusting for covariates, the hazard ratios for ischemic stroke (IS) in men aged <60 years were significant higher in participants with elevated BP, stage 1 hypertension, and stage 2 hypertension than normal BP (all P<0.05); an increased risk of intracerebral hemorrhage (ICH) was also observed for those with stage 2 hypertension. Similarly, in women aged, the risk of stroke increased for those with stage 2 hypertension both in <60 years and in ≥60 years. Moreover, more than 60% of incident strokes were attributed to systolic BP (SBP) ≥120mmHg and diastolic BP (DBP) <80mmHg in men aged <60 years. CONCLUSIONS: Elevated BP increases the risk of developing stroke, particularly in the absence of routine BP measurements and hypertension treatment. A strict BP management target (SBP, <120 mmHg; DBP, <80 mmHg) should be adopted for young and middle-aged men. METHODS: This population-based cohort study was conducted between October 1991 and January 2018. The association of BP categories, defined by the 2017 ACC/AHA BP guideline, with first-ever stroke risk was assessed using Cox regression models.

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PURPOSE: To compare the effects of airborne-particle abrasion protocols on the surface morphology, the phase transformation and the resin bond strength of highly translucent zirconia (M) and conventional zirconia (Z). METHODS: Thirteen groups (N = 12) of Z and M specimens were prepared. Except for the control group, the specimens were sandblasted with conditions involving different grit sizes (50 µm or 110 µm), treatment times (10 s or 20 s) and pressures (0.1 MPa, 0.3 MPa or 0.6 MPa). The surface morphology was analyzed using scanning electron microscope (SEM) and the phase analysis was conducted with X-ray diffraction (XRD). The Ra and the shear bond strength (SBS) were measured and statistically analyzed, and the failure mode was determined by optical microscope. RESULTS: The surface morphologies were strongly dependent on treatment conditions. Larger particle size and higher pressure resulted in higher Ra for both materials. Longer blasting time resulted in higher Ra for Z but not M. Overall, the SBS increased with increasing Ra; the highest average SBS was achieved by M and exceeded 18 MPa. The monoclinic transformation was not found in any treatment for M, but was found in Z. CONCLUSIONS: Z and M showed different dependence on the airborne-particle abrasion parameters in terms of Ra, SBS and phase transformation. The conditions for maximizing SBS included a 110 µm particle size and 20 s treatment for both, with pressures of 0.3 MPa and 0.6 MPa for the M and Z, respectively.

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Malignant hyperthermia is a pharmacogenetic disorder, which is an uncommon but frequently fatal intricacy of inhalation anesthesia in man. It causes a quick rise in body temperature to highly irreversible levels, which causes death in around three of four cases. The trigger anesthetics cause an anomalous, continued ascent in myoplasmic calcium levels. Possible mechanisms by which continuous release of sodium, calcium from skeletal muscle plasma membrane and sarcoplasmic reticulum stores respectively can produce the profound hyperthermia are discussed.

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Despite the wide applications, systematic mechanobiological investigation of 3D porous scaffolds has yet to be performed due to the lack of methodologies for decoupling the complex interplay between structural and mechanical properties. Here, we discover the regulatory effect of cryoprotectants on ice crystal growth and use this property to realize separate control of the scaffold pore size and stiffness. Fibroblasts and macrophages are sensitive to both structural and mechanical properties of the gelatin scaffolds, particularly to pore sizes. Interestingly, macrophages within smaller and softer pores exhibit pro-inflammatory phenotype, whereas anti-inflammatory phenotype is induced by larger and stiffer pores. The structure-regulated cellular mechano-responsiveness is attributed to the physical confinement caused by pores or osmotic pressure. Finally, in vivo stimulation of endogenous fibroblasts and macrophages by implanted scaffolds produce mechano-responses similar to the corresponding cells in vitro, indicating that the physical properties of scaffolds can be leveraged to modulate tissue regeneration.

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Plant embryos are generated and develop in a stable and well-protected microenvironment surrounded by maternal tissue, which is vital for embryogenesis. However, the signaling mechanisms responsible for maternal tissue-to-proembryo communication are not well understood. Here, we report a pathway for maternal tissue-to-proembryo communication. We identify a DELLA protein, NtCRF1 (NtCYS regulative factor 1), which regulates suspensor programmed cell death (PCD). NtCRF1 can bind to the promoter of NtCYS and regulate the suspensor PCD-switch module NtCYS-NtCP14 in response to gibberellin (GA). We confirm that GA4, as a primary signal triggering suspensor PCD, is generated in the micropylar endothelium by the transient activation of NtGA3oxs in the maternal tissue. Thus, we propose that GA is a maternal-to-proembryo communication signal that is decoded in the proembryo by a GID1-CRF1-CYS-CP14 signaling cascade. Using this mode of communication, maternal tissue precisely controls the embryonic suspensor PCD and is able to nurse the proembryo in a stage-dependent manner.

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Due to the climate change and human activity, the frequency and intensity of algal blooms have increased significantly. Recent studies have shown that during the bloom event, evaluated levels of cyanobacteria could infiltrate the drinking water treatment process and emerge in the filtered and disinfected water, thus threatening the safety of the drinking water supply. Among these concerned cyanobacteria, Microcystis aeruginosa is one of the most commonly detected species that cause algal bloom in a fresh water body. The present work was designed to investigate the transport and retention behaviour of Microcystis aeruginosa in a packed column to resolve the mechanisms that drive the transport behaviour of Microcystis under various operational conditions. The results showed that lab-cultured Microcystis aeruginosa could effectively break through the packed column regardless of ionic strength, media size or flow rate, as well as the presence of dissolved organic matter in the water under the conditions investigated. Such behaviour significantly contradicts those of fluorescent microspheres, which are commonly considered as ideal colloids. In addition, the combined impacts of pre-oxidation technologies and filtration on Microcystis aeruginosa removal were tested systematically. It was found that even the cells have been lysed/oxidized, no significant improvement of cell removals were observed in packed column. This paper provides a significant and comprehensive record of transport and retention behaviour of Microcystis aeruginosa in porous media. The results found herein suggest that in addition to the effort preventing toxin release/exposure during bloom events in source water, engineers and researchers should also pay attention to the transport and retention of Microcystis aeruginosa and other algal cells in filters to minimize the risk of breakthrough of cyanobacteria cells in the drinking water treatment process.

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A surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) is described for the quantitative analysis of the proteinic stroke biomarker S100-ß that has to be detected at very low concentration levels. The Raman reporter 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) on gold nanoparticles (GNPs) was employed as the SERS tags. They are shown to perform much better than bare GNPs in LF strips. The S100-ß protein can be detected by this method with very low detection limits by monitoring the intensity of the characteristic Raman peak of the S100-ß protein-conjugated GNPs at 1332 cm-1. Under optimized conditions, the assay works in the 1 pg·mL-1 to 40 ng·mL-1 S100-ß concentration range, and the detection limit is as low as 0.14 pg·mL-1. This is lower by a factor of 3 compared to colorimetric or fluorimetric methods. Graphical abstract Schematic illustration of the configuration (A) and the principle of the SERS-based lateral flow assay for quantification of S100-ß (B).

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